Lactobacillus reuteri is a heterofermentative bacterium that resides in the gastrointestinal tract of humans and animals. It is widely used as a dietary supplement. Valeur et al. show that L. reuteri colonized human gastrointestinal tract and positively modulated local immune cell populations as consequence of oral intake of L. reuteri tablets (Valeur et al. Colonization and Immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract. Appl. Environ/Microbiol. 2004 February; 70(2):1176-1181).
Lactobacillus plantarum is another probiotic bacterium. Klarin et al. show that L. plantarum is capable of surviving the passage from the stomach to the rectum and to adhere to the rectal mucosa also in patients treated with antibiotics. (Klarin et al. Adhesion of the probiotic bacterium Lactobacillus plantarum 299 on the gut mucosa in critically ill patients: a randomized open trial. Crit. Care 2005; 9(3): R285-293). Qin et al. studied the effects of enteral feeding of L. plantarum on the gut permeability and septic complications in the patients with acute pancreatitis. Enteral feeding of L. plantarum attenuated disease severity and improved the intestinal permeability. (Qin, H. L et al. Effect of Lactobacillus plantarum enteral feeding on the gut permeability and septic complications in the patients with acute pancreatic. Eur. J. CLin. Nutr. 2008 Jul; 62(7): 923-30). Hirose et al. show that heat-killed L. plantarum augments acquired immunity in healthy subjects. (Hirose, Y. et al. Daily intake of heat-killed Lactobacillus plantarum L-137 augments acquired immunity in healthy adults. J. Nutr. 2006 December; 136(12):3069-73). Van Baarlen et al. describe in vivo immune responses in duodenum of healthy humans after consumption of L. plantarum (van Baarlen P. et al. 2009. Differential NF-kB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc. Natl. Acad. Sci USA 2009. Feb. 17; 106(7): 2371-2376). Klarin et al. show that use of Lactobacillus plantarum reduces pathogenic bacterial load in the oropharynx of thracheally intubated, mechanically ventilated, critically ill patients. (Klarin et al. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomized controlled open pilot study. Crit. Care 2008, 12: R136).
Yet another probiotic bacterium is Lactobacillus rhamnosus GG. Vendt et al. showed that children fed with L. rhamnosus GG-enriched formula grew better than those fed with regular formula. (Vendt, N. et al. Growth during the first 6 months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial. J. Hum. Nutr. Diet. 2006 February; 19(1): 51-8). Another study shows that oral administration of Lactobacillus rhamnosus GG supplementation has a positive impact on Helicobacterium pylori therapy related side-effects and on overall treatment tolerability. (Armuzzi A. et al. Aliment Pharmacol Ther. 2001. February; 15(2): 163-9. Arvola et al. showed that oral intake of Lactobacillus GG reduced antibiotic associated diarrhea in children with respiratory infections. (Arvola T. et al. Prophylactic Lactobacillus GG reduces antibiotic associated diarrhea in children with respiratory infections: a randomized study. Pediatrics. 1999 November; 104(5): e64)
Lactobacillus casei is another probiotic bacterium that has been shown to have potential to enhance human natural killer cell activity when administered orally in the form of fermented milk. (Takeda K. et al. 2006, Clin. Exp. Immunol. October 146(1):109-115.) Takagi et al. showed that L. casei may be associated with tumor suppression (Takagi A. et al. 2008. J. Gastroenterol. 43(9):661-669). Aso et al. demonstrated preventive effect of L. casei preparation on the recurrence of superficial bladder cancer in a double-blind trial. (Aso. Y etala. 1995. Eur Urol. 27(2): 104-9.) Tormo Carnicer et al. showed that L. casei survives in the gastrointestinal tract and it affects on secretory immunoglobulin levels when orally taken. (Tormo Carnicer, R. et al. 2006. Intake of fermented milk containing Lactobacillus casei DN-114001 and its effect on gut flora. An. Pediatr (Barc). November 65(5):448-53.). Cobo Santz et al. demonstrated also that children receiving L. casei fermented milk has lower tendency and reduction of duration to incidence of infectious diseases. (Cobo Sanz J M. Et al. 2006. Nutr Hosp. July-0August; 21(4): 547-51). Beausoleil et al. show that fermented milk combining Lactobacillus acidophilus and L. casei prevent antibiotic-associated diarrhea. (Beausoleil et al. 2007. Effect of a fermented milk combining Lactobacillus acidophilus CL1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial. Can J. Gastroenterol. November 21(11):732-736.)
Lactobacillus acidophilus strains have been shown to be beneficial for patients suffering of irritable bowel syndrome (Sinn D. H. et al 2008. Therapeutic effect of Lactobacillus acidophilus-SDC 2012, 2013 in patients with irritable bowel syndrome. Dig Dis Sci. October 53 (10) 2714-8). Drago et al. showed a treatment of bacterial vaginosis with vaginal douche containing a strain of L. acidophilus to restore a normal vaginal environment. (Drago L. et al. 2007 Activity of a Lactobacillus acidophilus-based douche for the treatment of bacterial vaginosis. J. Altern. Complement. Med. May 13(4): 435-8.). Danducci F. et al showed that lyophilized and inactivated culture of Lactobacillus acidophilus increased Helicobacter pylori eradication in patients. (Danducci F. 2000. A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol. Ther. 2000 Dec. 14 (12): 1625-9).
Bifidobacterium infantis is a probiotic bacterium that inhabits in intestine of both infants and in adults. O'Mahony et al. showed that oral intake of B. infantis alleviated symptoms of irritable bowel syndrome. (O'Mahony et al. 2005. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology March; 128(3); 541-51). Some indications of reduced occurrence of nectortising enterocolitis has been found by providing live B. infantis bacteria to newborns (Hoyos A B. 1999 Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int. J. Infect. Dis. Summer; 3(4):197-202.). Similarly, there are indications that oral administration of live B. infantis may be an effective treatment for acute watery diarrhea (Vivatvakin B. 2006. J. Med Assoc.Thai. September; 89 Suppl 3:S126-133.).
Bifidobacterium longum has been shown to have potential to alleviate symptoms of ulcerative colitis (Furrie E. 2005 Synbiotic therapy (Bidifidobacteirum longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomized controlled pilot trial. Gut 2005 February; 54(2):242-249.). deVrese et al show that oral intake of Lactobacillus gasseri, Bifidobacterium longun and Bifidobacterium bifidum shorten common cold episodes and reduce the severity of the symptoms. (deVrese M. et al. 2005. Effect of Lactoballius gasseri PA 16/8, Bifidobacteruim longum sP07/3. B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin. Nutr. August; 24(4): 481-91). There is some evidence that bifidobacteria may affect immune response to poliovirus vaccination of infants. Mullie et al. found that antipoliovirus response was triggered with a fermented formula that contained Bifidobacterium longum, B. infantis and B. breve. (Mullie C. 2004. Increased poliovirus-specific intestinal antibody response coincides with promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in infants: a randomized, double-blind, placebo-controlled trial. Pediatr. Res November, 56(5): 791-5). Araki et al. demonstrated that oral administration of a Bifidobacterium breve-strain significantly decreased rotavirus shedding in stool samples and prevented rotavirus infection. (Araki K. et al. 1999. Kansenshogaku Casshi April; 73(4): 305-310).
U.S. Pat. No. 5,716,615 discloses a pharmaceutical composition containing at least two different lyophilized viable bacteria for treatment of chronic hepatitis following C virus infection.
N-acetyl-glucosamine (NAG) is a compound that exists naturally in the body. In various forms, this compound has been studied for its potential in alleviating some of the conditions associated with several diseases including osteoarthritis, inflammatory bowel disease and Crohn's disease and the inflammatory response in peritonitis (Gardiner, Dietary N-acetylglucosamine(GlcNAc): Absorption, Distribution, Metabolism, Excretion and Biological Activity, GlycoScience and Nutrition (2000) 1(9):1-3; Salvatore et al., A pilot Study of N-acetyl-glucosamine, a nutritional substrate for glycosaminoglycan synthesis in paediatric chronic inflammatory bowel disease, Alimentary Pharmacology and Therapeutics (2000) 14(12):1567-1579). GMDP (N-acetyl-D-glucosaminyl(beta.-1-4)-N-Acetyl-muramyl-L-ananyl-D-isoglutamine) in combination with NAG has been suggested as a treatment for Hepatitis C (U.S. Pat. No. 6,281,191).
In U.S. Pat. No. 8,007,783 we disclosed a method to treat hepatitis patients with a formulation that consists of lysate of freeze dried Lactobacillus delbrueckii subsp. Bulgaricus with N-acetyl glucosamine. Here we expand the method to formulations consisting of lysates of other freeze dried bacterial strains in combination of NAG.